Matches in SemOpenAlex for { <https://semopenalex.org/work/W4311679898> ?p ?o ?g. }
- W4311679898 abstract "Ca2+ influx through high-voltage-activated calcium channels (HVACCs) controls diverse cellular functions. A critical feature enabling a singular signal, Ca2+ influx, to mediate disparate functions is diversity of HVACC pore-forming α1 and auxiliary CaVβ1-CaVβ4 subunits. Selective CaVα1 blockers have enabled deciphering their unique physiological roles. By contrast, the capacity to post-translationally inhibit HVACCs based on CaVβ isoform is non-existent. Conventional gene knockout/shRNA approaches do not adequately address this deficit owing to subunit reshuffling and partially overlapping functions of CaVβ isoforms. Here, we identify a nanobody (nb.E8) that selectively binds CaVβ1 SH3 domain and inhibits CaVβ1-associated HVACCs by reducing channel surface density, decreasing open probability, and speeding inactivation. Functionalizing nb.E8 with Nedd4L HECT domain yielded Chisel-1 which eliminated current through CaVβ1-reconstituted CaV1/CaV2 and native CaV1.1 channels in skeletal muscle, strongly suppressed depolarization-evoked Ca2+ influx and excitation-transcription coupling in hippocampal neurons, but was inert against CaVβ2-associated CaV1.2 in cardiomyocytes. The results introduce an original method for probing distinctive functions of ion channel auxiliary subunit isoforms, reveal additional dimensions of CaVβ1 signaling in neurons, and describe a genetically-encoded HVACC inhibitor with unique properties." @default.
- W4311679898 created "2022-12-28" @default.
- W4311679898 creator A5000882661 @default.
- W4311679898 creator A5019452162 @default.
- W4311679898 creator A5027168303 @default.
- W4311679898 creator A5033796691 @default.
- W4311679898 creator A5034656890 @default.
- W4311679898 creator A5045437602 @default.
- W4311679898 creator A5048476359 @default.
- W4311679898 creator A5062850545 @default.
- W4311679898 creator A5070207038 @default.
- W4311679898 creator A5071356175 @default.
- W4311679898 creator A5088650922 @default.
- W4311679898 date "2022-12-09" @default.
- W4311679898 modified "2023-10-15" @default.
- W4311679898 title "Selective posttranslational inhibition of CaVβ1-associated voltage-dependent calcium channels with a functionalized nanobody" @default.
- W4311679898 cites W1528714879 @default.
- W4311679898 cites W1543942926 @default.
- W4311679898 cites W1595570385 @default.
- W4311679898 cites W1600158535 @default.
- W4311679898 cites W1601456560 @default.
- W4311679898 cites W1781961175 @default.
- W4311679898 cites W1921440755 @default.
- W4311679898 cites W1971439989 @default.
- W4311679898 cites W1971791499 @default.
- W4311679898 cites W1973150566 @default.
- W4311679898 cites W1977584840 @default.
- W4311679898 cites W1984987102 @default.
- W4311679898 cites W1985206041 @default.
- W4311679898 cites W1991280665 @default.
- W4311679898 cites W1993855785 @default.
- W4311679898 cites W1995610152 @default.
- W4311679898 cites W1998292458 @default.
- W4311679898 cites W2009291123 @default.
- W4311679898 cites W2009870936 @default.
- W4311679898 cites W2017824230 @default.
- W4311679898 cites W2023331462 @default.
- W4311679898 cites W2024567284 @default.
- W4311679898 cites W2025538209 @default.
- W4311679898 cites W2026530002 @default.
- W4311679898 cites W2035488746 @default.
- W4311679898 cites W2035885166 @default.
- W4311679898 cites W2037174767 @default.
- W4311679898 cites W2039319290 @default.
- W4311679898 cites W2041114576 @default.
- W4311679898 cites W2045617166 @default.
- W4311679898 cites W2057198039 @default.
- W4311679898 cites W2062212257 @default.
- W4311679898 cites W2063266439 @default.
- W4311679898 cites W2081040968 @default.
- W4311679898 cites W2082338288 @default.
- W4311679898 cites W2085223489 @default.
- W4311679898 cites W2086711528 @default.
- W4311679898 cites W2087098118 @default.
- W4311679898 cites W2088072568 @default.
- W4311679898 cites W2101072772 @default.
- W4311679898 cites W2104784898 @default.
- W4311679898 cites W2110808180 @default.
- W4311679898 cites W2112161053 @default.
- W4311679898 cites W2112163644 @default.
- W4311679898 cites W2113788562 @default.
- W4311679898 cites W2114120270 @default.
- W4311679898 cites W2115399420 @default.
- W4311679898 cites W2119586900 @default.
- W4311679898 cites W2120045671 @default.
- W4311679898 cites W2121501753 @default.
- W4311679898 cites W2123319286 @default.
- W4311679898 cites W2129103251 @default.
- W4311679898 cites W2129706672 @default.
- W4311679898 cites W2130186818 @default.
- W4311679898 cites W2134201060 @default.
- W4311679898 cites W2138773108 @default.
- W4311679898 cites W2138885636 @default.
- W4311679898 cites W2139389363 @default.
- W4311679898 cites W2139653729 @default.
- W4311679898 cites W2143459920 @default.
- W4311679898 cites W2144081223 @default.
- W4311679898 cites W2154905702 @default.
- W4311679898 cites W2159998111 @default.
- W4311679898 cites W2165912575 @default.
- W4311679898 cites W2170787296 @default.
- W4311679898 cites W2187921174 @default.
- W4311679898 cites W2297716557 @default.
- W4311679898 cites W2419494810 @default.
- W4311679898 cites W2551557276 @default.
- W4311679898 cites W2594927333 @default.
- W4311679898 cites W2778595920 @default.
- W4311679898 cites W2883919904 @default.
- W4311679898 cites W2898602871 @default.
- W4311679898 cites W2901480635 @default.
- W4311679898 cites W2967302504 @default.
- W4311679898 cites W2973457155 @default.
- W4311679898 cites W2977810099 @default.
- W4311679898 cites W3003002159 @default.
- W4311679898 cites W3093631525 @default.
- W4311679898 cites W3104957291 @default.
- W4311679898 cites W3137416125 @default.
- W4311679898 cites W3146868396 @default.
- W4311679898 cites W3202338629 @default.
- W4311679898 cites W4221080620 @default.